Genomic haploinsufficiency resulting from microdeletion involving 13 genes mapping to within chromosomal region 7q11.23 in a Williams-Beuren syndrome patient: Case report

• Autor(a) principal: Medina-Acosta, Enrique
• Data de Publicação: 2010
• Outros Autores: da Silva, Antonio Francisco Alves, Campos Fernandes, Regina Célia de Souza
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Revista Científica da Faculdade de Medicina de Campos
• Texto Completo: https://www.fmc.br/ojs/index.php/RCFMC/article/view/122
• topic: haploinsuficiência; microdeleção; microssatélite; síndrome de Williams-Beuren; STR; teste genético; haploinsufficiency; microdeletion; microsatellite; Williams-Beuren syndrome; STR; genetic test

Introduction: Williams-Beuren syndrome is a neurodevelopmental disorder that impacts multiple systems. The most frequent cause of Williams-Beuren syndrome is a submicroscopic deletion (0.2Mb to 2.5Mb) at 7q11.23 in the long arm of chromosome 7. The genetic condition hallmarking affected individuals is the genomic haploinsufficiency determined by the hemizygosity of contiguous genes. The genetic diagnosis cannot be done by banding G karyotyping because of the resolution limit (>5Mb) of the classic cytogenetic technique. The segmental rearrangement can be detected by in situ hybridization with DNA specific probes labeled with fluorochromes (FISH) or genotyping highly polymorphic microsatellite loci, and performing segregation analysis of alleles in nuclear families for verification of hemizygosity in the 7q11.23 region. Objectives: To report a case of Williams-Beuren syndrome with late diagnosis, emphasizing the advantages of the precise diagnostic confirmation by genotyping six microsatellite loci specific for the 7q11.23 chromosomal region, using Quantitative Fluorescence Polymerase Chain Reaction (QF-PCR).Methods: Case report and allelic genotyping using QF-PCR for six microsatellite loci at 7q11.23 region. Results: The phenotypic alterations led to the diagnostic hypothesis of Williams-Beuren syndrome. The child´s genotype exhibited loss of the expected heterozygosity in three informative microsatellite loci, which define a physical interval of 0.9 Mb, comprising 13 contiguous genes. The informative maternal alleles absent in the child´s genetic profile were D7SNUDIM3_227, D7SNUDIM6_303, D7SNUDIM11_242. The loss of the expected heterozygosity constitutes evidence of a microdeletion, characteristic in Williams-Beuren syndrome patients. Conclusions: Segregation analysis of parental alleles to the child revealed the presence of a segmental rearrangement involving a microdeletion of about one million base pairs in the chromosome 7 inherited from the mother, resulting in haploinsufficiency of at least 13 genes.